The epigenome, which controls cell identity and function, is not maintained with 100% fidelity in somatic animal cells. Errors in the maintenance of the epigenome lead to epigenetic drift, an important hallmark of aging. Numerous studies have described DNA methylation clocks that correlate epigenetic drift with increasing age. The question of how significant a role epigenetic drift plays in creating the phenotypes associated with aging remains open. A recent study describes a new DNA methylation clock that can be slowed by caloric restriction (CR) in a way that correlates with the degree of lifespan and healthspan extension conferred by CR, suggesting that epigenetic drift itself is a determinant of mammalian lifespan. Genetic transplantation using genomic editing of DNA methylation homeostatic genes from long-lived to short-lived species is one way to potentially demonstrate a causative role for DNA methylation. Whether the DNA methylation clock be reset to youthful state, eliminating the effects of epigenetic drift without requiring a pluripotent cell intermediate is a critical question with profound implications for the development of aging therapeutics. Methods that transiently erase the DNA methylation pattern of somatic cells may be developed that reset this aging hallmark with potentially profound effects on lifespan, if DNA methylation-based epigenetic drift really plays a primary role in aging.
Keywords: DNA methylation; aging; epigenetic drift; epigenetics; epigenome; lifespan; stem cells.